Gnanakaran S, García Angel E
Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA.
Proteins. 2005 Jun 1;59(4):773-82. doi: 10.1002/prot.20439.
The force fields used in classical modeling studies are semiempirical in nature and rely on their validation by comparison of simulations with experimental data. The all-atom replica-exchange molecular dynamics (REMD) methodology allows us to calculate the thermodynamics of folding/unfolding of peptides and small proteins, and provides a way of evaluating the reliability of force fields. We apply the REMD to obtain equilibrium folding/unfolding thermodynamics of a 21-residue peptide containing only alanine residues in explicit aqueous solution. The thermodynamics of this peptide is modeled with both the OPLS/AA/L and the A94/MOD force fields. We find that the helical content and the values for the helix propagation and nucleation parameters for this alanine peptide are consistent with measurements on similar peptides and with calculations using the modified AMBER force field (A94/MOD). The nature of conformations, both folded and unfolded, that contributes to the helix-coil transition profile, however, is quite different between these two force fields.
经典建模研究中使用的力场本质上是半经验性的，并且依赖于通过将模拟结果与实验数据进行比较来进行验证。全原子副本交换分子动力学（REMD）方法使我们能够计算肽和小蛋白质折叠/去折叠的热力学，并提供了一种评估力场可靠性的方法。我们应用REMD来获得在明确的水溶液中仅含丙氨酸残基的21个残基肽的平衡折叠/去折叠热力学。该肽的热力学用OPLS/AA/L和A94/MOD力场进行建模。我们发现，该丙氨酸肽的螺旋含量以及螺旋延伸和成核参数的值与对类似肽的测量结果以及使用改进的AMBER力场（A94/MOD）进行的计算结果一致。然而，这两个力场之间，对螺旋-卷曲转变曲线有贡献的折叠和未折叠构象的性质却大不相同。
